Expression of interleukin-32 in bone marrow of patients with myeloma and its prognostic significance

Abstract

BACKGROUNDThe guiding effect of prognostic stratification in multiple myeloma (MM) for treatment has been increasingly emphasized in recent years. The stratification of risk factors based on the International Staging System (ISS), Durie-Salmon (DS) staging and related indicators is affected by the renal function of patients, resulting in poor performance. This study assesses the relationship between interleukin-32 (IL-32) and related risk factors in 67 patients with MM and their clinical outcomes.AIMTo investigate the feasibility of IL-32 in evaluating prognosis in patients with MM and the factors influencing prognosis.METHODSThis was a pragmatic, prospective observational study of patients with MM at a single center. According to IL-32 level, patients were divided into two groups. The variables under consideration included age, blood β2-microglobulin, albumin, C-reactive protein, serum calcium, serum creatinine, lactate dehydrogenase, M protein type, ISS stage, DS stage, and IL-32 levels and minimal residual disease (MRD) after induction treatment. The main outcomes were progression-free survival (PFS) and overall survival (OS).RESULTSIL-32 was an important factor affecting PFS and OS in patients with MM. Compared with patients with IL-32 levels ≥ 856.4 pg/mL, patients with IL-32 levels < 856.4 pg/mL had longer PFS (P = 0.0387) and OS (P = 0.0379); Univariate analysis showed that IL-32 level and MRD were significantly associated with OS and PFS (P < 0.05). Multivariate analysis showed that IL-32 levels ≥ 856.4 pg/mL and MRD positive were still independent risk factors for OS and PFS (P < 0.05).CONCLUSIONIL-32 is valuable for assessing the prognosis of MM patients. IL-32 level combined with MRD may be a useful routine evaluation index for MM patients after treatment.

Monoclonal Gammopathies and the Bone Marrow Microenvironment: From Bench to Bedside and Then Back Again

“…In addition, both chemokines affect the macrophages’ infiltration and polarization into TAM in BM [ 162 ]. Along the same lines, another soluble factor, IL-32, has been linked with worse survival and a more advanced clinical stage of MM [ 163 , 164 ]. Indeed IL-32α induces IL-6 production in BM stromal cells which in turn promotes MM cell growth and prevents apoptosis through JAK/STAT and RAS/MAPKs pathway activation [ 165 , 166 ].…”

Immunological Prognostic Factors in Multiple Myeloma

“…This has also been confirmed by another study [ 60 ], showing the high expression of the IL-32 gene in plasma cells, which was much higher in MM patients and correlated with worse survival and more advanced clinical stage of the disease [ 59 ]. Another analysis showed [ 61 ] that patients with lower IL-32 levels had more positive PFS and OS. In addition, the correlation between minimal residual disease (MRD) and IL-32 has been analysed in patients, as MRD is important in predicting disease recurrence and evaluating therapy.…”

“…In addition, the correlation between minimal residual disease (MRD) and IL-32 has been analysed in patients, as MRD is important in predicting disease recurrence and evaluating therapy. It has been shown [ 61 ] that MRD and high levels of IL-32 have great prognostic utility for patients, possibly enabling the early identification of resistant MM cells in patients with complete disease remission.…”

KDM2A Targets PFKFB3 for Ubiquitylation to Inhibit the Proliferation and Angiogenesis of Multiple Myeloma Cells

“…In addition, vascular endothelial growth factor (VEGF) is a key component of pro-angiogenic activity, and our previous study also demonstrated that IL-32 promoted angiogenesis. In consideration of high expression of IL-32 in multiple myeloma (25,26), we then measured the levels of VEGF and IL-32 in MM cells by ELISA. As expected, the median levels of VEGF and IL-32 were higher in the shKDM2A group than in the control group (Figure 3B).…”